Cholesterol and the body

Cholesterol and triglycerides – both essential for many of our body’s functions – cannot float freely in the blood. Our blood is more akin to water, and remember that water and fat don’t mix well together. Consequently these fats are packaged in spherical particles called lipoproteins to be “trafficked” from one place to another. These particles have names, LDL and HDL being the best recognized. LDL cholesterol, or LDL-C, is what most doctors refer to when they tell you your level of “bad” cholesterol. This number tells us how much cholesterol is carried in your LDL particles. It is especially important in some cholesterol abnormalities, the most important one being FH. The higher the number, the greater the risk of an adverse event such as a heart attack or stroke. The lower the number, the lower your risk. HDL-C is the other key cholesterol number you will often hear your doctor mention. Typically, the higher the HDL-C the lower your risk of one of the aforementioned events. Unfortunately, a high HDL-C does not guarantee freedom from a heart attack or stroke. In fact, it is no longer clear to doctors that raising the HDL-C with medications will lower our patient risks. Consequently, LDL is the main “target” that doctors attack in order to diminish their patients’ risk.

Interestingly, most of the cholesterol we carry in our blood has not been consumed in our food. Actually we make our own cholesterol, and every cell in the body can do so. Our liver though is the most important organ for cholesterol production and removal. When our liver fails to function properly, our cholesterol numbers can be exceedingly high and dangerous.

What is Familial Hypercholesterolemia?

FH is short for Familial Hypercholesterolemia. It is an inherited disorder that leads to aggressive and premature cardiovascular disease. This includes problems like heart attacks, strokes, and even narrowing of our heart valves. For individuals with FH, although diet and lifestyle are important, they are not the cause of high LDL. In FH patients, genetic mutations make the liver incapable of metabolizing (or removing) excess LDL. The result is very high LDL levels which can lead to premature cardiovascular disease (CVD). 

Did you know?

The vast majority of the cholesterol circulating in a person’s body is produced by the liver. Cholesterol is a necessary component in the structure and function of human cells. Individuals with FH are unable to recycle this natural supply of cholesterol that their bodies are constantly producing. Therefore, the cholesterol levels of an individual with FH are exceedingly high. Over time the elevated blood cholesterol can lead to blockages in the arteries of the heart and/or brain. The longer a person experiences high LDL-C, the more likely he or she will be to experience a CV event. As FH is a genetic disorder, even when affected children are still in their mother’s womb they are “bathing” in their own high cholesterol. The process of vascular disease therefore can have its origins even prior to our children’s birth.

There are two forms of FH. If you have inherited this genetic mutation from one parent, then you will have Heterozygous FH (HeFH). HeFH occurs in 1 in 250 people worldwide. If you inherit FH from both parents, it is much more severe in its consequences. This form of FH is called Homozygous FH (HoFH). It is very rare, occurring in about 1 in 160,000 to one million people worldwide.

We measure blood cholesterol in milligrams per deciliter (mg/dL).

Adults with FH may have untreated LDL-C levels that range from 190mg/dL to 400mg/dL or even higher. Children with FH generally have LDL-C levels above 160mg/dL, but in pre-teens, levels can be even lower.

  • High HDL-C levels are desirable and somewhat protect against coronary heart disease (CHD).
  • High LDL-C levels are undesirable and contribute to CHD risk.

Triglycerides, another blood fat, come from the diet and are also produced in the liver. When extremely elevated, triglycerides can cause pancreatitis and can also increase the risk of developing CHD. High triglycerides are generally not present in people with FH. 

Click here to view the FH diagnostic criteria.

Living with FH

FH facts

About 1 in 250 people worldwide have FH.

In the United States alone, an estimated 1.3 million people live with FH. Yet only 10% of them are diagnosed. Can you imagine? Nearly 2 million people in the US might have FH and not even know it. Perhaps they won’t know it until they have a heart attack! This is what we want to change!

  • Over 90% of people with FH have not been properly diagnosed. (1)
  • FH runs in families. If one parent has FH, each child has a 50% chance of having FH. (2)
  • 1 in 250 people in the world have FH. (1)
  • An estimated 1.3 million people in the U.S. have FH. (1)
  • If left untreated, men have a 50% rise of having a heart attack by age 50. Untreated women have a 30% risk by age 60(3)
  • 1 in 160,000 to 1 in 1 million people have HoFH.  (1)
  • FH is even more common in certain populations such as French Canadians, Ashkenazi Jews, Lebanese, and South African Afrikaners. In these populations FH may be found as frequently as 1 in every 67 people.

1. Nordestgaard B G et al. Eur Heart J: 2013, 34:3478-3490
2. Goldstein JL et al. Familial hypercholesterolemia. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York: McGraw-Hill; 2001:2863-2913
3. Marks D, Thorogood M, Neil HA et al. A review on the diagnosis, natural history, and treatment of familial hypercholesterolemia. Athersclerosis 2003;168:1-14.

What is HoFH?

HoFH is a rare but exceedingly aggressive form of FH. If both parents have FH, there is a 25% chance that their child or children will have HoFH (along with a 50% chance that their children will have HeFH). However, if a child is diagnosed with HoFH, that means both parents have some form of FH.

HoFH leads to aggressive atherosclerosis (narrowing and blocking of blood vessels). This process starts even before birth and progresses rapidly. It can affect the coronary arteries, carotid arteries, aorta, and aortic valve . If left untreated, heart attack or sudden death are likely to occur as early as the teenage years. 

Family with FH

Woman with FH

What can I do?

FH is treatable! If FH is found early, serious problems of the heart and blood vessels may be prevented or dramatically delayed by taking steps to protect yourself. These include:

  • Not smoking.
  • Exercising regularly.
  • Eating a healthy diet low in saturated and trans fats.
  • Taking medications.
  • Going on LDL-apheresis.

Nearly 100% of people with FH will require cholesterol-lowering medications. For some people with FH, more aggressive measures are needed, including LDL-apheresis (a very simple procedure in which LDL-C cholesterol is removed from the blood on a weekly or biweekly basis.)

The American Academy of Pediatrics recommends that if a family has a pattern of early heart attacks or heart disease defined as before age 55 for men and 65 for women, children in that family should have cholesterol testing after the age of 2 years and before age 10.

  • It is important to find FH and take action at any age, because when treated, the risk of heart disease can be reduced to levels similar to those of the general population.